Bioc L04 Sex Linked and Mitochondrial Inheritance Flashcards
What mechanism ensures males and females have the same expression levels of X linked genes?
X-inactivation
What is the Lyon Hypothesis?
One X chromosome is inactivated in every female somatic cell. This occurs early in embryonic development and is random unless one copy is damaged in which case the damaged X chromosome will be inactivated.
What are Barr bodies?
How many Barry bodies are present per cell?
Dense mass of chromatin in interphase of somatic cells that is not observed in males.
Barr Bodies = # of X chromosomes -1
So 0 for males, 1 in Klinefelter syndrome (47, XXY)
What is the mechanism of X inactivation?
What escapes inactivation?
Gene XIST is expressed at the X-inactivation center and its mRNA coats the chromosome it’s on to inactivate it. the XIST gene doesn’t inactivate itself and is only expressed by the inactive chromosome
Inactivation is stabilized by high DNA methylation and histone hyposacetylation.
XHIST gene and PAR1/1 (psudatosomal genes)
What is sex-linked inheritance?
How does X linked inheritance differ in males and females?
What’s the difference between X-linked recessive disease in males and females?
Genes passed on X or Y chromosomes, no vital genes on Y chromosome
It behaves like autosomal inheritance in females, males only get one copy which will be dominant.
Much more common in males because if their X chromosome is disease carrying, they will have the disease, while females need two copies of the diseased allele have the disease
What can exclude X-linked recessive inheritance when looking at a family gene?
Father to son transmission. Fathers don’t pass on an X chromosome.
note: the disease can skip generations with female carriers.
What will the offspring inheritance be from mating of carrier female (X1X2) + normal male (X1Y)
punnett squares can help with to determine..
Daighters: half normal, half carriers
Sons: half normal, half diseased
What will the offspring inheritance be from mating of normal female (X1X1) + affected male (X2Y)
All daughters and sons will be normal, father is the only carrier and does not pass on his X chromosome
What will the offspring inheritance be from mating of carrier female (X1X2) + affected male (X2Y)?
Daughters: half diseased, half carriers
Sons: half normal, half diseased
What are some examples of X-linked recessive diseases?
- Hemophilia A (factor VIII deficiency)
- Hemophilia B (factor IX deficiency)
- G6PD deficiency
- Ornithine transcarbamylase (OTC) deficiency
- Red-green color blindness
- Lesch-Nyhan syndrome
- Duchenne muscular dystrophy / Becker muscular dystrophy
- Red-green color blindness, (usually the result of aberrant recombination when seen in females?)
What is Duchenne muscular dystrohpy (DMD)?
How is Becker Muscular Dystrophy different?
How is it inherited?
How can females show symptoms of the disease?
Caused by a mutation in dystrophin gene (largest gene in genome) leading to weakness, muscle loss and high serum creatine levels. Most cases are from large deletions resulting in complete absence of the gene.
Less severe forms (Becker muscular dystrophy) are caused milder mutations that result in a partially active protein.
It is an X-linked recessive disease.
Only 8-10% of female carriers show signs of muscle weakness because of random X-inactivation
How does X-linked dominant inheritance differ from X-linked recessive inheritance? How is it similar?
It differs in that it is much more frequent in females than males. Similar in that there is still no father to son transmission but %100 transmission from fathers to daughters.
There is a vertical transmission pattern because only one copy of the diseased allele is required in males or females to exhibit the disease
What’s an example of X-linked dominant inheritance?
What is genetic anticipation?
How is this disease an exception to the female pattern of inheritence?
(few relative cases)
Fragile X syndrome from a mutated FMR1 gene, symptoms include mental retardation, distinct facial features.
“Anticipation is a phenomenon whereby the symptoms of a genetic disorder become apparent at an earlier age as it is passed on to the next generation, in most cases with an increase in symptoms”
The disease shows reduced penetrence in females, an exception to X-linked dominant diseases being more common in females.
What is a sex-linked trait?
What is a sex-influenced trait? and some examples
What is a sex-limited trait?
A sex-linked trait is caused by genes on the X or Y chromosome
A sex-influenced trait is an autosomal trait expressed more frequently in one sex than another. Ex: male pattern baldness, gout, hereditary hemochromatosis ( excess iron accumulation, women less affected because of menstruation)
A sex-limited trait is an autosomal trait expressed only by one sex. This is due to anatomical but not genetic differences. Ex: sperm motility problems
What is Mitochondrial inheritance?
What is mtDNA
Mitochondrial inheritence is the inheritence of mitochondrial DNA (mtDNA).
mtDNA consists of 37 genes, mostly involving oxidative phosphorylation and the genes reside w/in mitochondria
